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Studies of differential gene expression in advanced carotid atherosclerosis

Objective

Atherosclerosis accounts for the majority of brain infarctions and it is a chronic process that is converted into an acute syndrome when a lesion ruptures and triggers thrombosis. The risk profile of advanced atherogenesis is signalled by markers of enhanced prothrombotic capacity, attenuated fibrinolysis and defective coagulation. Patients with more than 3 procoagulant risk conditions have carotid stenosis or show progression of pre-existing stenosis during a 5-year period. Inflammation, local fibrinogenesis /fibrinolysis and intraplaque remodelling significantly contributes towards atherosclerotic plaque rupture.

Molecular mechanisms leading to the above processes remains controversial. Because risk factor control is not enough to detain the atherosclerotic process, we aim to search of new genes that may be differentially expressed by advanced carotid lesion. Using PALM micro-laser technology we will be able to differentiate areas and also individual cells within the plaque over-expressing studied genes. Results obtained will be compared to corresponding plaque protein expression and related plasma circulating molecules and studied biochemical parameters. Patients clinical subgroups will be formed based on symptomatic disease, presence of VRF and plaque stability/histology type.

To identify molecular mechanisms leading to symptomatic carotid disease by studying differential gene expression in the advanced carotid plaque selected genes of interest identified in previous studies will be analysed by RT-PCR: TF, TFP I, MMP-2, MMP-8, MMP-9, COX-2, PLA2, LRP, Caveoline, Bax, Bcl2. Further, gene and protein de-regulation will be examined in serum and tissue specimens. Genes of interest will be selected and their protein expression will be studied in plaque homogenates and selected areas of plaque tissue. We hope to describe the role of identified markers in mediating cellular damage/activation, plaque progression and instability resulting in symptomatic carotid disease.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/basic medicine/immunology
  • /medical and health sciences/clinical medicine/cardiology/cardiovascular diseases/arteriosclerosis

Call for proposal

FP6-2002-MOBILITY-11
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Funding Scheme

ERG - Marie Curie actions-European Re-integration Grants

Coordinator

CONSORCI INSTITUT CATALÀ DE CIÈNCIES CARDIOVASCULARS
Address
Av. S.antoni M.claret 167
Barcelona
Spain